Epstein–Barr virus

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus 

 

Human gammaherpesvirus 4
Electron micrograph of two Epstein–Barr virions (viral particles) showing round capsids loosely surrounded by the membrane envelope
Virus classification
(unranked):	Virus
Realm:	Duplodnaviria
Kingdom:	Heunggongvirae
Phylum:	Peploviricota
Class:	Herviviricetes
Order:	Herpesvirales
Family:	Herpesviridae
Genus:	Lymphocryptovirus
Species:	Human gammaherpesvirus 4
Synonyms[1]
Epstein-Barr virus Human herpesvirus 4 HHV-4 EBV

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.

It is best known as the cause of infectious mononucleosis ("mono" or "glandular fever"). It is also associated with various non-malignant, premalignant, and malignant Epstein–Barr virus-associated lymphoproliferative diseases such as Burkitt lymphoma, hemophagocytic lymphohistiocytosis, and Hodgkin's lymphoma; non-lymphoid malignancies such as gastric cancer and nasopharyngeal carcinoma; and conditions associated with human immunodeficiency virus such as hairy leukoplakia and central nervous system lymphomas. The virus is also associated with the childhood disorders of Alice in Wonderland syndrome and acute cerebellar ataxia and, based on some evidence, higher risks of developing certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. About 200,000 cancer cases globally per year are thought to be attributable to EBV.

Infection with EBV occurs by the oral transfer of saliva and genital secretions. Most people become infected with EBV and gain adaptive immunity. In the United States, about half of all five-year-old children and about 90% of adults have evidence of previous infection. Infants become susceptible to EBV as soon as maternal antibody protection disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and other developed countries, many people are not infected with EBV in their childhood years. When infection with EBV occurs during adolescence, it causes infectious mononucleosis 35 to 50% of the time.

EBV infects B cells of the immune system and epithelial cells. Once EBV's initial lytic infection is brought under control, EBV latency persists in the individual's B cells for the rest of their life.

Virology

Simplified diagram of the structure of EBV

Structure and genome

The virus is about 122–180 nm in diameter and is composed of a double helix of deoxyribonucleic acid (DNA) which contains about 172,000 base pairs and 85 genes. The DNA is surrounded by a protein nucleocapsid, which is surrounded by a tegument made of protein, which in turn is surrounded by an envelope containing both lipids and surface projections of glycoproteins, which are essential to infection of the host cell. In July 2020, a team of researchers reported the first complete atomic model of the nucleocapsid of the virus. This "first complete atomic model [includes] the icosahedral capsid, the capsid-associated tegument complex (CATC) and the dodecameric portal--the viral genome translocation apparatus."

Tropism

The term viral tropism refers to which cell types that EBV infects. EBV can infect different cell types, including B cells and epithelial cells.

The viral three-part glycoprotein complexes of gHgL gp42 mediate B cell membrane fusion; although the two-part complexes of gHgL mediate epithelial cell membrane fusion. EBV that are made in the B cells have low numbers of gHgLgp42 complexes, because these three-part complexes interact with Human-leukocyte-antigen class II molecules present in B cells in the endoplasmic reticulum and are degraded. In contrast, EBV from epithelial cells are rich in the three-part complexes because these cells do not normally contain HLA class II molecules. As a consequence, EBV made from B cells are more infectious to epithelial cells, and EBV made from epithelial cells are more infectious to B cells. Viruses lacking the gp42 portion are able to bind to human B cells, but unable to infect.

Replication cycle

The EBV replication cycle

Entry to the cell

EBV can infect both B cells and epithelial cells. The mechanisms for entering these two cells are different.

To enter B cells, viral glycoprotein gp350 binds to cellular receptor CD21 (also known as CR2). Then, viral glycoprotein gp42 interacts with cellular MHC class II molecules. This triggers fusion of the viral envelope with the cell membrane, allowing EBV to enter the B cell. Human CD35, also known as complement receptor 1 (CR1), is an additional attachment factor for gp350/220, and can provide a route for entry of EBV into CD21-negative cells, including immature B-cells. EBV infection downregulates expression of CD35.

To enter epithelial cells, viral protein BMRF-2 interacts with cellular β1 integrins. Then, viral protein gH/gL interacts with cellular αvβ6/αvβ8 integrins. This triggers fusion of the viral envelope with the epithelial cell membrane, allowing EBV to enter the epithelial cell. Unlike B-cell entry, epithelial-cell entry is actually impeded by viral glycoprotein gp42.

Once EBV enters the cell, the viral capsid dissolves and the viral genome is transported to the cell nucleus.

Lytic replication

The lytic cycle, or productive infection, results in the production of infectious virions. EBV can undergo lytic replication in both B cells and epithelial cells. In B cells, lytic replication normally only takes place after reactivation from latency. In epithelial cells, lytic replication often directly follows viral entry.

For lytic replication to occur, the viral genome must be linear. The latent EBV genome is circular, so it must linearize in the process of lytic reactivation. During lytic replication, viral DNA polymerase is responsible for copying the viral genome. This contrasts with latency, in which host-cell DNA polymerase copies the viral genome.

Lytic gene products are produced in three consecutive stages: immediate-early, early, and late. Immediate-early lytic gene products act as transactivators, enhancing the expression of later lytic genes. Immediate-early lytic gene products include BZLF1 (also known as Zta, EB1, associated with its product gene ZEBRA) and BRLF1 (associated with its product gene Rta). Early lytic gene products have many more functions, such as replication, metabolism, and blockade of antigen processing. Early lytic gene products include BNLF2. Finally, late lytic gene products tend to be proteins with structural roles, such as VCA, which forms the viral capsid. Other late lytic gene products, such as BCRF1, help EBV evade the immune system.

EGCG, a polyphenol in green tea, has shown in a study to inhibit EBV spontaneous lytic infection at the DNA, gene transcription, and protein levels in a time- and dose-dependent manner; the expression of EBV lytic genes Zta, Rta, and early antigen complex EA-D (induced by Rta), however, the highly stable EBNA-1 gene found across all stages of EBV infection is unaffected. Specific inhibitors (to the pathways) suggest that Ras/MEK/MAPK pathway contributes to EBV lytic infection though BZLF1 and PI3-K pathway through BRLF1, the latter completely abrogating the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection. Additionally, the activation of some genes but not others is being studied to determine just how to induce immune destruction of latently infected B-cells by use of either TPA or sodium butyrate.

Latency

Unlike lytic replication, latency does not result in production of virions. Instead, the EBV genome circular DNA resides in the cell nucleus as an episome and is copied by cellular DNA polymerase. In latency, only a portion of EBV's genes are expressed. Latent EBV expresses its genes in one of three patterns, known as latency programs. EBV can latently persist within B cells and epithelial cells, but different latency programs are possible in the two types of cell.

EBV can exhibit one of three latency programs: Latency I, Latency II, or Latency III. Each latency program leads to the production of a limited, distinct set of viral proteins and viral RNAs.

Gene Expressed	EBNA-1	EBNA-2	EBNA-3A	EBNA-3B	EBNA-3C	EBNA-LP	LMP-1	LMP-2A	LMP-2B	EBER
Product	Protein	Protein	Protein	Protein	Protein	Protein	Protein	Protein	Protein	ncRNAs
Latency I	+	–	–	–	–	–	–	–	–	+
Latency II	+	–	–	–	–	+	+	+	+	+
Latency III	+	+	+	+	+	+	+	+	+	+

Also, a program is postulated in which all viral protein expression is shut off (Latency 0).

Within B cells, all three latency programs are possible. EBV latency within B cells usually progresses from Latency III to Latency II to Latency I. Each stage of latency uniquely influences B cell behavior. Upon infecting a resting naive B cell, EBV enters Latency III. The set of proteins and RNAs produced in Latency III transforms the B cell into a proliferating blast (also known as B cell activation). Later, the virus restricts its gene expression and enters Latency II. The more limited set of proteins and RNAs produced in Latency II induces the B cell to differentiate into a memory B cell. Finally, EBV restricts gene expression even further and enters Latency I. Expression of EBNA-1 allows the EBV genome to replicate when the memory B cell divides.

Within epithelial cells, only Latency II is possible.

In primary infection, EBV replicates in oropharyngeal epithelial cells and establishes Latency III, II, and I infections in B-lymphocytes. EBV latent infection of B-lymphocytes is necessary for virus persistence, subsequent replication in epithelial cells, and release of infectious virus into saliva. EBV Latency III and II infections of B-lymphocytes, Latency II infection of oral epithelial cells, and Latency II infection of NK- or T-cell can result in malignancies, marked by uniform EBV genome presence and gene expression.

Reactivation

Latent EBV in B cells can be reactivated to switch to lytic replication. This is known to happen in vivo, but what triggers it is not known precisely. In vitro, latent EBV in B cells can be reactivated by stimulating the B cell receptor, so reactivation in vivo probably takes place when latently infected B cells respond to unrelated infections. In vitro, latent EBV in B cells can also be reactivated by treating the cells with sodium butyrate or 12-O-Tetradecanoylphorbol-13-acetate.

Transformation of B-lymphocytes

When EBV infects B cells in vitro, lymphoblastoid cell lines eventually emerge that are capable of indefinite growth. The growth transformation of these cell lines is the consequence of viral protein expression.

EBNA-2, EBNA-3C, and LMP-1 are essential for transformation, whereas EBNA-LP and the EBERs are not.

Following natural infection with EBV, the virus is thought to execute some or all of its repertoire of gene expression programs to establish a persistent infection. Given the initial absence of host immunity, the lytic cycle produces large numbers of virions to infect other (presumably) B-lymphocytes within the host.

The latent programs reprogram and subvert infected B-lymphocytes to proliferate and bring infected cells to the sites at which the virus presumably persists. Eventually, when host immunity develops, the virus persists by turning off most (or possibly all) of its genes, only occasionally reactivating to produce fresh virions. A balance is eventually struck between occasional viral reactivation and host immune surveillance removing cells that activate viral gene expression.

The site of persistence of EBV may be bone marrow. EBV-positive patients who have had their own bone marrow replaced with bone marrow from an EBV-negative donor are found to be EBV-negative after transplantation.

Latent antigens

All EBV nuclear proteins are produced by alternative splicing of a transcript starting at either the Cp or Wp promoters at the left end of the genome (in the conventional nomenclature). The genes are ordered EBNA-LP/EBNA-2/EBNA-3A/EBNA-3B/EBNA-3C/EBNA-1 within the genome.

The initiation codon of the EBNA-LP coding region is created by an alternate splice of the nuclear protein transcript. In the absence of this initiation codon, EBNA-2/EBNA-3A/EBNA-3B/EBNA-3C/EBNA-1 will be expressed depending on which of these genes is alternatively spliced into the transcript.

Protein/genes

Protein/gene/antigen	Stage	Description
EBNA-1	latent+lytic	EBNA-1 protein binds to a replication origin (oriP) within the viral genome and mediates replication and partitioning of the episome during division of the host cell. It is the only viral protein expressed during group I latency.
EBNA-2	latent+lytic	EBNA-2 is the main viral transactivator.
EBNA-3	latent+lytic	These genes also bind the host RBP-Jκ protein.
LMP-1	latent	LMP-1 is a six-span transmembrane protein that is also essential for EBV-mediated growth transformation.
LMP-2	latent	LMP-2A/LMP-2B are transmembrane proteins that act to block tyrosine kinase signaling.
EBER	latent	EBER-1/EBER-2 are small nuclear RNAs, which bind to certain nucleoprotein particles, enabling binding to PKR (dsRNA-dependent serin/threonin protein kinase), thus inhibiting its function. EBERs are by far the most abundant EBV products transcribed in EBV infected cells. They are commonly used as targets for the detection of EBV in histological tissues. ER-particles also induce the production of IL-10, which enhances growth and inhibits cytotoxic T-cells.
v-snoRNA1	latent	Epstein–Barr virus snoRNA1 is a box CD-snoRNA generated by the virus during latency. V-snoRNA1 may act as a miRNA-like precursor that is processed into 24 nucleotide sized RNA fragments that target the 3'UTR of viral DNA polymerase mRNA.
ebv-sisRNA	latent	Ebv-sisRNA-1 is a stable intronic sequence RNA generated during latency program III. After the EBERs, it is the third-most abundant small RNA produced by the virus during this program.
miRNAs	latent	EBV microRNAs are encoded by two transcripts, one set in the BART gene and one set near the BHRF1 cluster. The three BHRF1 pri-miRNAS (generating four miRNAs) are expressed during type III latency, whereas the large cluster of BART miRNAs (up to 20 miRNAs) are expressed during type II latency. The functions of these miRNAs are currently unknown.
EBV-EA	lytic	early antigen
EBV-MA	lytic	membrane antigen
EBV-VCA	lytic	viral capsid antigen
EBV-AN	lytic	alkaline nuclease

Subtypes of EBV

EBV can be divided into two major types, EBV type 1 and EBV type 2. These two subtypes have different EBNA-3 genes. As a result, the two subtypes differ in their transforming capabilities and reactivation ability. Type 1 is dominant throughout most of the world, but the two types are equally prevalent in Africa. One can distinguish EBV type 1 from EBV type 2 by cutting the viral genome with a restriction enzyme and comparing the resulting digestion patterns by gel electrophoresis.

Role in disease

Main article: Infectious mononucleosis

EBV causes infectious mononucleosis.^[38] Children infected with EBV have few symptoms or can appear asymptomatic, but when infection is delayed to adolescence or adulthood, it can cause fatigue, fever, inflamed throat, swollen lymph nodes in the neck, enlarged spleen, swollen liver, or rash. Post-infectious chronic fatigue syndrome has also been associated with EBV infection.

EBV has also been implicated in several other diseases, including Burkitt's lymphoma, hemophagocytic lymphohistiocytosis, Hodgkin's lymphoma, stomach cancer, nasopharyngeal carcinoma, multiple sclerosis, and lymphomatoid granulomatosis. Specifically, EBV infected B-cells have been shown to reside within the brain lesions of multiple sclerosis patients. Additional diseases that have been linked to EBV include Gianotti–Crosti syndrome, erythema multiforme, acute genital ulcers, oral hairy leukoplakia. The viral infection is also associated with, and often contributes to the development of, a wide range of non-malignant lymphoproliferative diseases such as severe hypersensitivity mosquito bite allergy reactions, Epstein-Barr virus-positive mucocutaneous ulcers, and hydroa vacciniforme as well as malignant lymphoproliferative diseases such as Epstein–Barr virus-positive Burkitt lymphoma, Epstein–Barr virus-positive Hodgkin lymphoma, and primary effusion lymphoma.

The Epstein–Barr virus has been implicated in disorders related to alpha-synuclein aggregation (e.g. Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy).

History

The Epstein–Barr virus was named after Michael Anthony Epstein and Yvonne Barr, who discovered the virus together with Bert Achong. In 1961, Epstein, a pathologist and expert electron microscopist, attended a lecture on "The Commonest Children's Cancer in Tropical Africa—A Hitherto Unrecognised Syndrome" by Denis Parsons Burkitt, a surgeon practicing in Uganda, in which Burkitt described the "endemic variant" (pediatric form) of the disease that bears his name. In 1963, a specimen was sent from Uganda to Middlesex Hospital to be cultured. Virus particles were identified in the cultured cells, and the results were published in The Lancet in 1964 by Epstein, Achong, and Barr. Cell lines were sent to Werner and Gertrude Henle at the Children's Hospital of Philadelphia who developed serological markers. In 1967, a technician in their laboratory developed mononucleosis and they were able to compare a stored serum sample, showing that antibodies to the virus developed. In 1968, they discovered that EBV can directly immortalize B cells after infection, mimicking some forms of EBV-related infections,^[60] and confirmed the link between the virus and infectious mononucleosis.

Research

As a relatively complex virus, EBV is not yet fully understood. Laboratories around the world continue to study the virus and develop new ways to treat the diseases it causes. One popular way of studying EBV in vitro is to use bacterial artificial chromosomes. Epstein–Barr virus can be maintained and manipulated in the laboratory in continual latency (a property shared with Kaposi's sarcoma-associated herpesvirus, another of the eight human herpesviruses). Although many viruses are assumed to have this property during infection of their natural hosts, there is not an easily managed system for studying this part of the viral lifecycle. Genomic studies of EBV have been able to explore lytic reactivation and regulation of the latent viral episome.

Although under active research, an Epstein–Barr virus vaccine is not yet available. The development of an effective vaccine could prevent up to 200,000 cancers globally per year. Like other human herpesvirus' Epstein-Barr might allow eradication via a course of the pro-drug valaciclovir, but further research is needed to determine if eradication is actually achievable. Antiviral agents act by inhibiting viral DNA replication, but there is little evidence that they are effective against Epstein–Barr virus. Moreover, they are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects.

 

History of herbalism

From Wikipedia, the free encyclopedia

The history of herbalism is closely tied with the history of medicine from prehistoric times up until the development of the germ theory of disease in the 19th century. Modern medicine from the 19th century to today has been based on evidence gathered using the scientific method. Evidence-based use of pharmaceutical drugs, often derived from medicinal plants, has largely replaced herbal treatments in modern health care. However, many people continue to employ various forms of traditional or alternative medicine. These systems often have a significant herbal component. The history of herbalism also overlaps with food history, as many of the herbs and spices historically used by humans to season food yield useful medicinal compounds,^[1][2] and use of spices with antimicrobial activity in cooking is part of an ancient response to the threat of food-borne pathogens.^[3]

Prehistory

The use of plants as medicines predates written human history. Archaeological evidence indicates that humans were using medicinal plants during the Paleolithic, approximately 60,000 years ago. (Furthermore, other non-human primates are also known to ingest medicinal plants to treat illness) Plant samples gathered from prehistoric burial sites have been thought to support the claim that Paleolithic people had knowledge of herbal medicine. For instance, a 60,000-year-old Neanderthal burial site, "Shanidar IV", in northern Iraq has yielded large amounts of pollen from 8 plant species, 7 of which are used now as herbal remedies. More recently Paul B. Pettitt has written that "A recent examination of the microfauna from the strata into which the grave was cut suggests that the pollen was deposited by the burrowing rodent Meriones tersicus, which is common in the Shanidar microfauna and whose burrowing activity can be observed today". Medicinal herbs were found in the personal effects of Ötzi the Iceman, whose body was frozen in the Ötztal Alps for more than 5,000 years. These herbs appear to have been used to treat the parasites found in his intestines.

Ancient history

The Ebers Papyrus (c. 1550 BCE) from ancient Egypt has a prescription for Cannabis sativa (marijuana) applied topically for inflammation.

Mesopotamia

In Mesopotamia, the written study of herbs dates back over 5,000 years to the Sumerians, who created clay tablets with lists of hundreds of medicinal plants (such as myrrh and opium).

Ancient Egypt

Ancient Egyptian texts are of particular interest due to the language and translation controversies that accompany texts from this era and region. These differences in conclusions stem from the lack of complete knowledge of the Egyptian language: many translations are composed of mere approximations between Egyptian and modern ideas, and there can never be complete certainty of meaning or context. While physical documents are scarce, texts such as the Papyrus Ebers serve to illuminate and relieve some of the conjecture surrounding ancient herbal practices. The Papyrus consists of lists of ailments and their treatments, ranging from "disease of the limbs" to "diseases of the skin" and has information on over 850 plant medicines, including garlic, juniper, cannabis, castor bean, aloe, and mandrake. Treatments were mainly aimed at ridding the patient of the most prevalent symptoms because the symptoms were largely regarded as the disease itself. Knowledge of the collection and preparation of such remedies are mostly unknown, as many of the texts available for translation assume the physician already has some knowledge of how treatments are conducted and therefore such techniques would not need restating. Though modern understanding of Egyptian herbals stem form the translation of ancient texts, there is no doubt that trade and politics carried the Egyptian tradition to regions across the world, influencing and evolving many cultures medical practices and allowing for a glimpse into the world of ancient Egyptian medicine. Herbs used by Egyptian healers were mostly indigenous in origin, although some were imported from other regions like Lebanon. Other than papyri, evidence of herbal medicine has also been found in tomb illustrations or jars containing traces of herbs.

India

In India, Ayurveda medicine has used many herbs such as turmeric possibly as early as 4,000 BC. Earliest Sanskrit writings such as the Rig Veda, and Atharva Veda are some of the earliest available documents detailing the medical knowledge that formed the basis of the Ayurveda system. Many other herbs and minerals used in Ayurveda were later described by ancient Indian herbalists such as Charaka and Sushruta during the 1st millennium BC. The Sushruta Samhita attributed to Sushruta in the 6th century BC describes 700 medicinal plants, 64 preparations from mineral sources, and 57 preparations based on animal sources.

China

In China, seeds likely used for herbalism have been found in the archaeological sites of Bronze Age China dating from the Shang Dynasty. The mythological Chinese emperor Shennong is said to have written the first Chinese pharmacopoeia, the "Shennong Ben Cao Jing". The "Shennong Ben Cao Jing" lists 365 medicinal plants and their uses - including Ephedra (the shrub that introduced the drug ephedrine to modern medicine), hemp, and chaulmoogra (one of the first effective treatments for leprosy). Succeeding generations augmented on the Shennong Bencao Jing, as in the Yaoxing Lun (Treatise on the Nature of Medicinal Herbs), a 7th-century Tang Dynasty treatise on herbal medicine.

Ancient Greece and Rome

Hippocrates

The Hippocratic Corpus serves as a collection of texts that are associated with the 'Father of Western Medicine', Hippocrates of Kos. Though the actual authorship of some of these texts is disputed, each reflects the general ideals put forth by Hippocrates and his followers. The recipes and remedies included in parts of the Corpus no doubt reveal popular and prevalent treatments of the early ancient Greek period.

Though any of the herbals included in the Corpus are similar to those practiced in the religious sectors of healing, they differ strikingly in the lack of rites, prayers, or chants used in the application of remedies. This distinction is truly indicative of the Hippocratic preference for logic and reason within the practices of medicine.

The ingredients mentioned in the Corpus consist of a myriad of herbs, both local to Greece and imported from exotic locales such as Arabia. While many imported goods would have been too expensive for common household use, some of the suggested ingredients include the more common and cheaper elderberries and St. John's Wort.

Galen

Galen of Pergamon, a Greek physician practicing in Rome, was certainly prolific in his attempt to write down his knowledge on all things medical – and in his pursuit, he wrote many texts regarding herbs and their properties, most notably his Works of Therapeutics. In this text, Galen outlines the merging of each discipline within medicine that combine to restore health and prevent disease. While the subject of therapeutics encompasses a wide array of topics, Galen's extensive work in the humors and four basic qualities helped pharmacists to better calibrate their remedies for the individual person and their unique symptoms.

Diocles of Carystus

The writings of Diocles of Carystus were also extensive and prolific in nature. With enough prestige to be referred to as "the second Hippocrates", his advice in herbalism and treatment was to be taken seriously. Though the original texts no longer exist, many medical scholars throughout the ages have quoted Diocles rather extensively, and it is in these fragments that we gain knowledge of his writings. It is purported that Diocles actually wrote the first comprehensive herbal- this work then cited numerous times by contemporaries such as Galen, Celsus, and Soranus.

Pliny

In what is one of the first encyclopedic texts, Pliny the Elder's Natural History serves as a comprehensive guide to nature and also presents an extensive catalog of herbs valuable in medicine. With over 900 drugs and plants listed, Pliny's writings provide a very large knowledge base upon which we may learn more about ancient herbalism and medical practices. Pliny himself referred to ailments as "the greatest of all the operations of nature," and the act of treatment via drugs as impacting the "state of peace or of war which exists between the various departments of nature".

Dioscorides

Much like Pliny, Pedanius Dioscorides constructed a pharmacopeia, De Materia Medica, consisting of over 1000 medicines produced form herbs, minerals, and animals. The remedies that comprise this work were widely utilized throughout the ancient period and Dioscorides remained the greatest expert on drugs for over 1,600 years.

Similarly important for herbalists and botanists of later centuries was Theophrastus' Historia Plantarum, written in the 4th century BC, which was the first systematization of the botanical world.

Middle Ages

Further information: Medicine in the medieval Islamic world

While there are certainly texts from the medieval period that denote the uses of herbs, there has been a long-standing debate between scholars as to the actual motivations and understandings that underline the creation of herbal documents during the medieval period. The first point of view dictates that the information presented in these medieval texts were merely copied from their classical equivalents without much thought or understanding. The second viewpoint, which is gaining traction among modern scholars, states that herbals were copied for actual use and backed by genuine understanding.

Some evidence for the suggestion that herbals were utilized with knowledgeable intent, was the addition of several chapters of plants, lists of symptoms, habitat information, and plant synonyms added to texts such as the Herbarium. Notable texts utilized in this time period include Bald's Leechbook, the Lacnunga, the peri didaxeon, Herbarium Apulei, Da Taxone, and Madicina de Quadrupedidus, while the most popular during this time period were the Ex Herbis Femininis, the Herbarius, and works by Dioscorides.

Benedictine monasteries were the primary source of medical knowledge in Europe and England during the Early Middle Ages. However, most of these monastic scholars' efforts were focused on translating and copying ancient Greco-Roman and Arabic works, rather than creating substantial new information and practices. Many Greek and Roman writings on medicine, as on other subjects, were preserved by hand copying of manuscripts in monasteries. The monasteries thus tended to become local centers of medical knowledge, and their herb gardens provided the raw materials for simple treatment of common disorders. At the same time, folk medicine in the home and village continued uninterrupted, supporting numerous wandering and settled herbalists. Among these were the "wise-women" and "wise men", who prescribed herbal remedies often along with spells, enchantments, divination and advice. One of the most famous women in the herbal tradition was Hildegard of Bingen. A 12th-century Benedictine nun, she wrote a medical text called Causae et Curae. During this time, herbalism was mainly practiced by women, particularly among Germanic tribes.

There were three major sources of information on healing at the time including the Arabian School, Anglo-Saxon leechcraft, and Salerno. A great scholar of the Arabian School was Avicenna, who wrote The Canon of Medicine which became the standard medical reference work of the Arab world. "The Canon of Medicine is known for its introduction of systematic experimentation and the study of physiology, the discovery of contagious diseases and sexually transmitted diseases, the introduction of quarantine to limit the spread of infectious diseases, the introduction of experimental medicine, clinical trials, and the idea of a syndrome in the diagnosis of specific diseases. ...The Canon includes a description of some 760 medicinal plants and the medicine that could be derived from them." With Leechcraft, though bringing to mind part of their treatments, leech was the English term for medical practitioner. Salerno was a famous school in Italy centered around health and medicine. A student of the school was Constantine the African, credited with bringing Arab medicine to Europe.

Translation of herbals

Main article: Herbal

Dioscorides’ Materia Medica, c. 1334 copy in Arabic, describes medicinal features of cumin and dill.

During the Middle Ages, the study of plants began to be based on critical observations. "In the 16th and 17th century an interest in botany revived in Europe and spread to America by way of European conquest and colonization." Philosophers started to act as herbalists and academic professors studied plants with great depth. Herbalists began to explore the use of plants for both medicinal purposes and agricultural uses. Botanists in the Middle Ages were known as herbalists; they collected, grew, dried, stored, and sketched plants. Many became experts in identifying and describing plants according to their morphology and habitats, as well as their usefulness. These books, called herbals included beautiful drawings and paintings of plants as well as their uses.

At that time both botany and the art of gardening stressed the utility of plants for man; the popular herbal, described the medical uses of plants. During the Middle Ages, there was an expansion of book culture that spread through the medieval world. The phenomenon of translation is well-documented, from its beginnings as a scholarly endeavor in Baghdad as early as the eighth century to its expansion throughout European Mediterranean centers of scholarship by the eleventh and twelfth centuries. The process of translation is collaborative effort, requiring a variety of people to translate and add to them. However, how the Middle Ages viewed nature seems to be a mystery.

Translation of text and image has provided numerous versions and compilations of individual manuscripts from diverse sources, old and new. Translation is a dynamic process as well as a scholarly endeavor that contributed great to science in the Middle Ages; the process naturally entailed continuous revisions and additions. The Benedictine monasteries were known for their in-depth knowledge of herbals. These gardens grew the herbs which were considered to be useful for the treatment of the various human ills; the beginnings of modern medical education can be connected with monastic influence. Monastic academies were developed and monks were taught how to translate Greek manuscripts into Latin.

Knowledge of medieval botanicals was closely related to medicine because the plant's principal use was for remedies. Herbals were structured by the names of the plants, identifying features, medicinal parts of plant, therapeutic properties, and some included instructions on how to prepare and use them. For medical use of herbals to be effective, a manual was developed. Dioscorides' De material medica was a significant herbal designed for practical purposes.

Theophrastus wrote more than 200 papers describing the characteristics of over 500 plants. He developed a classification system for plants based on their morphology such as their form and structure. He described in detail pepper, cinnamon, bananas, asparagus, and cotton. Two of his best-known works, Enquiry into Plants and The Causes of Plants, have survived for many centuries and were translated into Latin. He has been referred to as the "grandfather of botany". Crateuas was the first to produce a pharmacological book for medicinal plants, and his book influenced medicine for many centuries. A Greek physician, Pedanius Dioscorides described over 600 different kinds of plants and describes their useful qualities for herbal medicine, and his illustrations were used for pharmacology and medicine as late as the Renaissance years.

Monasteries established themselves as centers for medical care. Information on these herbals and how to use them was passed on from monks to monks, as well as their patients. These illustrations were of no use to everyday individuals; they were intended to be complex and for people with prior knowledge and understanding of herbal. The usefulness of these herbals have been questioned because they appear to be unrealistic and several plants are depicted claiming to cure the same condition, as “the modern world does not like such impression." When used by experienced healers, these plants can provide their many uses. For these medieval healers, no direction was needed their background allowed them to choose proper plants to use for a variety of medical conditions. The monk's purpose was to collect and organize text to make them useful in their monasteries. Medieval monks took many remedies from classical works and adapted them to their own needs as well as local needs. This may be why none of the collections of remedies we have presently agrees fully with another.

Another form of translation was oral transmission; this was used to pass medical knowledge from generation to generation. A common misconception is that one can know early medieval medicine simply by identifying texts, but it is difficult to compose a clear understanding of herbals without prior knowledge. There are many factors that played in influenced in the translation of these herbals, the act of writing or illustrating was just a small piece of the puzzle, these remedies stems from many previous translations the incorporated knowledge from a variety of influences.

Early modern era

The 16th and 17th centuries were the great age of herbals, many of them available for the first time in English and other languages rather than Latin or Greek. The 18th and 19th centuries saw more incorporation of plants found in the Americas, but also the advance of modern medicine.

16th century

The first herbal to be published in English was the anonymous Grete Herball of 1526. The two best-known herbals in English were The Herball or General History of Plants (1597) by John Gerard and The English Physician Enlarged (1653) by Nicholas Culpeper. Gerard's text was basically a pirated translation of a book by the Belgian herbalist Dodoens and his illustrations came from a German botanical work. The original edition contained many errors due to faulty matching of the two parts. Culpeper's blend of traditional medicine with astrology, magic, and folklore was ridiculed by the physicians of his day, yet his book - like Gerard's and other herbals - enjoyed phenomenal popularity. The Age of Exploration and the Columbian Exchange introduced new medicinal plants to Europe. The Badianus Manuscript was an illustrated Mexican herbal written in Nahuatl and Latin in the 16th century.

17th century

The second millennium, however, also saw the beginning of a slow erosion of the pre-eminent position held by plants as sources of therapeutic effects. This began with the Black Death, which the then dominant Four Element medical system proved powerless to stop. A century later, Paracelsus introduced the use of active chemical drugs (like arsenic, copper sulfate, iron, mercury, and sulfur).

18th century

In the Americas, herbals were relied upon for most medical knowledge with physicians being few and far between. These books included almanacs, Dodoens' New Herbal, Edinburgh New Dispensatory, Buchan's Domestic Medicine, and other works. Aside from European knowledge on American plants, Native Americans shared some of their knowledge with colonists, but most of these records were not written and compiled until the 19th century. John Bartram was a botanist that studied the remedies that Native Americans would share and often included bits of knowledge of these plants in printed almanacs.

19th century

The formalization of pharmacology in the 19th century led to greater understanding of the specific actions drugs have on the body. At that time, Samuel Thompson was an uneducated but well respected herbalist who influenced professional opinions so much that Doctors and Herbalists would refer to themselves as Thompsonians. They distinguished themselves from "regular" doctors of the time who used calomel and bloodletting, and led to a brief renewal of the empirical method in herbal medicine.

Modern era

Traditional herbalism has been regarded as a method of alternative medicine in the United States since the Flexner Report of 1910 led to the closing of the eclectic medical schools where botanical medicine was exclusively practiced. In China, Mao Zedong reintroduced Traditional Chinese Medicine, which relied heavily on herbalism, into the health care system in 1949. Since then, schools have been training thousands of practitioners – including Americans – in the basics of Chinese medicines to be used in hospitals. While Britain in the 1930s was experiencing turbulence over the practice of herbalism, in the United States, government regulation began to prohibit the practice.

"The World Health Organization estimated that 80% of people worldwide rely on herbal medicines for some part of their primary health care. In Germany, about 600 to 700 plant based medicines are available and are prescribed by some 70% of German physicians."

The practice of prescribing treatments and cures to patients requires a legal medical license in the United States of America, and the licensing of these professions occurs on a state level. "There is currently no licensing or certification for herbalists in any state that precludes the rights of anyone to use, dispense, or recommend herbs."

"Traditional medicine is a complex network of interaction of both ideas and practices, the study of which requires a multidisciplinary approach." Many alternative physicians in the 21st century incorporate herbalism in traditional medicine due to the diverse abilities plants have and their low number of side effects.

Hippocratic Oath

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Hippocratic_Oath

 

The Greek physician Hippocrates (460–370 BC), to whom the oath is traditionally attributed

The Hippocratic Oath is an oath of ethics historically taken by physicians. It is one of the most widely known of Greek medical texts. In its original form, it requires a new physician to swear, by a number of healing gods, to uphold specific ethical standards. The oath is the earliest expression of medical ethics in the Western world, establishing several principles of medical ethics which remain of paramount significance today. These include the principles of medical confidentiality and non-maleficence. As the seminal articulation of certain principles that continue to guide and inform medical practice, the ancient text is of more than historic and symbolic value. Swearing a modified form of the oath remains a rite of passage for medical graduates in many countries, and is a requirement enshrined in legal statutes of various jurisdictions, such that violations of the oath may carry criminal or other liability beyond the oath's symbolic nature.

The original oath was written in Ionic Greek, between the fifth and third centuries BC. Although it is traditionally attributed to the Greek doctor Hippocrates and it is usually included in the Hippocratic Corpus, most modern scholars do not regard it as having been written by Hippocrates himself.

Text of the oath

Earliest surviving copy

A fragment of the oath on the 3rd-century Papyrus Oxyrhynchus 2547.

The oldest partial fragments of the oath date to circa AD 275.  The oldest extant version dates to roughly the 10th-11th century, held in the Vatican Library. A commonly cited version, dated to 1595, appears in Koine Greek with a Latin translation. In this translation, the author translates "πεσσὸν" to the Latin "fœtum."

The Hippocratic Oath, in Greek, from the 1923 Loeb edition, and then followed by the English translation:

ὄμνυμι Ἀπόλλωνα ἰητρὸν καὶ Ἀσκληπιὸν καὶ Ὑγείαν καὶ Πανάκειαν καὶ θεοὺς πάντας τε καὶ πάσας, ἵστορας ποιεύμενος, ἐπιτελέα ποιήσειν κατὰ δύναμιν καὶ κρίσιν ἐμὴν ὅρκον τόνδε καὶ συγγραφὴν τήνδε:

ἡγήσεσθαι μὲν τὸν διδάξαντά με τὴν τέχνην ταύτην ἴσα γενέτῃσιν ἐμοῖς, καὶ βίου κοινώσεσθαι, καὶ χρεῶν χρηΐζοντι μετάδοσιν ποιήσεσθαι, καὶ γένος τὸ ἐξ αὐτοῦ ἀδελφοῖς ἴσον ἐπικρινεῖν ἄρρεσι, καὶ διδάξειν τὴν τέχνην ταύτην, ἢν χρηΐζωσι μανθάνειν, ἄνευ μισθοῦ καὶ συγγραφῆς, παραγγελίης τε καὶ ἀκροήσιος καὶ τῆς λοίπης ἁπάσης μαθήσιος μετάδοσιν ποιήσεσθαι υἱοῖς τε ἐμοῖς καὶ τοῖς τοῦ ἐμὲ διδάξαντος, καὶ μαθητῇσι συγγεγραμμένοις τε καὶ ὡρκισμένοις νόμῳ ἰητρικῷ, ἄλλῳ δὲ οὐδενί.

διαιτήμασί τε χρήσομαι ἐπ᾽ ὠφελείῃ καμνόντων κατὰ δύναμιν καὶ κρίσιν ἐμήν, ἐπὶ δηλήσει δὲ καὶ ἀδικίῃ εἴρξειν.

οὐ δώσω δὲ οὐδὲ φάρμακον οὐδενὶ αἰτηθεὶς θανάσιμον, οὐδὲ ὑφηγήσομαι συμβουλίην τοιήνδε: ὁμοίως δὲ οὐδὲ γυναικὶ πεσσὸν φθόριον δώσω.

ἁγνῶς δὲ καὶ ὁσίως διατηρήσω βίον τὸν ἐμὸν καὶ τέχνην τὴν ἐμήν.

οὐ τεμέω δὲ οὐδὲ μὴν λιθιῶντας, ἐκχωρήσω δὲ ἐργάτῃσιν ἀνδράσι πρήξιος τῆσδε.

ἐς οἰκίας δὲ ὁκόσας ἂν ἐσίω, ἐσελεύσομαι ἐπ᾽ ὠφελείῃ καμνόντων, ἐκτὸς ἐὼν πάσης ἀδικίης ἑκουσίης καὶ φθορίης, τῆς τε ἄλλης καὶ ἀφροδισίων ἔργων ἐπί τε γυναικείων σωμάτων καὶ ἀνδρῴων, ἐλευθέρων τε καὶ δούλων.

ἃ δ᾽ ἂν ἐνθεραπείῃ ἴδω ἢ ἀκούσω, ἢ καὶ ἄνευ θεραπείης κατὰ βίον ἀνθρώπων, ἃ μὴ χρή ποτε ἐκλαλεῖσθαι ἔξω, σιγήσομαι, ἄρρητα ἡγεύμενος εἶναι τὰ τοιαῦτα.

ὅρκον μὲν οὖν μοι τόνδε ἐπιτελέα ποιέοντι, καὶ μὴ συγχέοντι, εἴη ἐπαύρασθαι καὶ βίου καὶ τέχνης δοξαζομένῳ παρὰ πᾶσιν ἀνθρώποις ἐς τὸν αἰεὶ χρόνον: παραβαίνοντι δὲ καὶ ἐπιορκέοντι, τἀναντία τούτων.

I swear by Apollo Healer, by Asclepius, by Hygieia, by Panacea, and by all the gods and goddesses, making them my witnesses, that I will carry out, according to my ability and judgment, this oath and this indenture.

To hold my teacher in this art equal to my own parents; to make him partner in my livelihood; when he is in need of money to share mine with him; to consider his family as my own brothers, and to teach them this art, if they want to learn it, without fee or indenture; to impart precept, oral instruction, and all other instruction to my own sons, the sons of my teacher, and to indentured pupils who have taken the Healer’s oath, but to nobody else.

I will use those dietary regimens which will benefit my patients according to my greatest ability and judgment, and I will do no harm or injustice to them. Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course. Similarly I will not give to a woman a pessary to cause abortion. But I will keep pure and holy both my life and my art. I will not use the knife, not even, verily, on sufferers from stone, but I will give place to such as are craftsmen therein.

Into whatsoever houses I enter, I will enter to help the sick, and I will abstain from all intentional wrong-doing and harm, especially from abusing the bodies of man or woman, bond or free. And whatsoever I shall see or hear in the course of my profession, as well as outside my profession in my intercourse with men, if it be what should not be published abroad, I will never divulge, holding such things to be holy secrets.

Now if I carry out this oath, and break it not, may I gain for ever reputation among all men for my life and for my art; but if I break it and forswear myself, may the opposite befall me. – Translation by W.H.S. Jones.

"First do no harm"

Main article: Primum non nocere

It is often said that the exact phrase "First do no harm" (Latin: Primum non nocere) is a part of the original Hippocratic oath. Although the phrase does not appear in the AD 245 version of the oath, similar intentions are vowed by, "I will abstain from all intentional wrong-doing and harm". The phrase primum non nocere is believed to date from the 17th century.

Another equivalent phrase is found in Epidemics, Book I, of the Hippocratic school: "Practice two things in your dealings with disease: either help or do not harm the patient". The exact phrase is believed to have originated with the 19th-century English surgeon Thomas Inman.

Context and interpretation

A 12th-century Greek manuscript of the oath

The oath is arguably the best known text of the Hippocratic Corpus, although most modern scholars do not attribute it to Hippocrates himself, estimating it to have been written in the fourth or fifth century BC. Alternatively, classical scholar Ludwig Edelstein proposed that the oath was written by the Pythagoreans, an idea that others questioned for lack of evidence for a school of Pythagorean medicine. While Pythagorean philosophy displays a correlation to the Oath's values, the proposal of a direct relationship has been mostly discredited in more recent studies. 

Its general ethical principles are also found in other works of the Corpus: the Physician mentions the obligation to keep the 'holy things' of medicine within the medical community (i.e. not to divulge secrets); it also mentions the special position of the doctor with regard to his patients, especially women and girls. However, several aspects of the oath contradict patterns of practice established elsewhere in the Corpus. Most notable is its ban on the use of the knife, even for small procedures such as lithotomy, even though other works in the Corpus provide guidance on performing surgical procedures.

Providing poisonous drugs would certainly have been viewed as immoral by contemporary physicians if it resulted in murder. However, the absolute ban described in the oath also forbids euthanasia. Several accounts of ancient physicians willingly assisting suicides have survived. Multiple explanations for the prohibition of euthanasia in the oath have been proposed: it is possible that not all physicians swore the oath, or that the oath was seeking to prevent widely held concerns that physicians could be employed as political assassins.

The interpreted AD 275 fragment of the oath contains a prohibition of abortion that is in contradiction to original Hippocratic text On the Nature of the Child, which contains a description of an abortion, without any implication that it was morally wrong, and descriptions of abortifacient medications are numerous in the ancient medical literature. While many Christian versions of the Hippocratic Oath, particularly from the middle-ages, explicitly prohibited abortion, the prohibition is often omitted from many oaths taken in US medical schools today, though it remains controversial. Scribonius Largus was adamant in AD 43 (the earliest surviving reference to the oath) that it preclude abortion.

As with Scribonius Largus, there seemed to be no question to Soranus that the Hippocratic Oath prohibits abortion, although apparently not all doctors adhered to it strictly in his time. According to Soranus' 1st or 2nd century AD work Gynaecology, one party of medical practitioners banished all abortives as required by the Hippocratic Oath; the other party—to which he belonged—was willing to prescribe abortions, but only for the sake of the mother's health.

The oath stands out among comparable ancient texts on medical ethics and professionalism through its heavily religious tone, a factor which makes attributing its authorship to Hippocrates particularly difficult. Phrases such as 'but I will keep pure and holy both my life and my art' suggest a deep, almost monastic devotion to the art of medicine. He who keeps to the oath is promised 'reputation among all men for my life and for my art'. This contrasts heavily with Galenic writings on professional ethics, which employ a far more pragmatic approach, where good practice is defined as effective practice, without reference to deities.

The oath's importance among the medical community is nonetheless attested by its appearance on the tombstones of physicians, and by the fourth century AD it had come to stand for the medical profession.

The oath continued to be in use in the Byzantine Christian world with its references to pagan deities replaced by a Christian preamble, as in the 12th-century manuscript pictured in the shape of a cross.

Modern versions and relevance

An engraving of Hippocrates by Peter Paul Rubens, 1638

The Hippocratic Oath has been eclipsed as a document of professional ethics by more extensive, regularly updated ethical codes issued by national medical associations, such as the AMA Code of Medical Ethics (first adopted in 1847), and the British General Medical Council's Good Medical Practice. These documents provide a comprehensive overview of the obligations and professional behaviour of a doctor to their patients and wider society. Doctors who violate these codes may be subjected to disciplinary proceedings, including the loss of their license to practice medicine. Nonetheless, the length of these documents has made their distillations into shorter oaths an attractive proposition. In light of this fact, several updates to the oath have been offered in modern times, some facetious.

The oath has been modified numerous times.

In the United States, the majority of osteopathic medical schools use the Osteopathic Oath in place of or in addition to the Hippocratic Oath. The Osteopathic Oath was first used in 1938, and the current version has been in use since 1954.

One of the most significant revisions was first drafted in 1948 by the World Medical Association (WMA), called the Declaration of Geneva. "During the post World War II and immediately after its foundation, the WMA showed concern over the state of medical ethics in general and over the world. The WMA took up the responsibility for setting ethical guidelines for the world's physicians. It noted that in those years the custom of medical schools to administer an oath to its doctors upon graduation or receiving a license to practice medicine had fallen into disuse or become a mere formality". In Nazi Germany, medical students did not take the Hippocratic Oath, although they knew the ethic of "nil nocere"—do no harm.

In the 1960s, the Hippocratic Oath was changed to require "utmost respect for human life from its beginning", making it a more secular obligation, not to be taken in the presence of any gods, but before only other people. When the oath was rewritten in 1964 by Louis Lasagna, Academic Dean of the School of Medicine at Tufts University, the prayer was omitted, and that version has been widely accepted and is still in use today by many US medical schools:

I swear to fulfill, to the best of my ability and judgment, this covenant:

I will respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow.

I will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism.

I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon's knife or the chemist's drug.

I will not be ashamed to say "I know not", nor will I fail to call in my colleagues when the skills of another are needed for a patient's recovery.

I will respect the privacy of my patients, for their problems are not disclosed to me that the world may know. Most especially must I tread with care in matters of life and death. If it is given me to save a life, all thanks. But it may also be within my power to take a life; this awesome responsibility must be faced with great humbleness and awareness of my own frailty. Above all, I must not play at God.

I will remember that I do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person's family and economic stability. My responsibility includes these related problems, if I am to care adequately for the sick.

I will prevent disease whenever I can, for prevention is preferable to cure.

I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.

If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.

In a 1989 survey of 126 US medical schools, only three of them reported use of the original oath, while thirty-three used the Declaration of Geneva, sixty-seven used a modified Hippocratic Oath, four used the Oath of Maimonides, one used a covenant, eight used another oath, one used an unknown oath, and two did not use any kind of oath. Seven medical schools did not reply to the survey.

As of 1993, only 14 per cent of medical oaths prohibited euthanasia, and only 8 per cent prohibited abortion.

In a 2000 survey of US medical schools, all of the then extant medical schools administered some type of profession oath. Among schools of modern medicine, sixty-two of 122 used the Hippocratic Oath, or a modified version of it. The other sixty schools used the original or modified Declaration of Geneva, Oath of Maimonides, or an oath authored by students and or faculty. All nineteen osteopathic schools used the Osteopathic Oath.

In France, it is common for new medical graduates to sign a written oath.

In 1995, Sir Joseph Rotblat, in his acceptance speech for the Nobel Peace Prize, suggested a Hippocratic Oath for Scientists.

In 2007 US citizen Rafiq Abdus Sabir was convicted for making a pledge to Al Qaeda thus agreeing to provide medical aid to wounded terrorists.

Violation

There is no direct punishment for breaking the Hippocratic Oath, although an arguable equivalent in modern times is medical malpractice, which carries a wide range of punishments, from legal action to civil penalties. In the United States, several major judicial decisions have made reference to the classical Hippocratic Oath, either upholding or dismissing its bounds for medical ethics: Roe v. Wade, Washington v. Harper, Compassion in Dying v. State of Washington (1996), and Thorburn v. Department of Corrections (1998). In antiquity, the punishment for breaking the Hippocratic oath could range from a penalty to losing the right to practice medicine.